Project Summary/ Abstract Although antiretroviral therapy (ART) holds remarkable promise for efficacious treatment of HIV infection, as well as for large-scale prevention through a ?treatment as prevention? (TasP) strategy, a gap exists between this potential and actual engagement in care across the cascade? thus undermining realization of this promise. Today, only one third of people in sub-Saharan Africa (SSA) have been tested for HIV, and 30% to 60% of patients are lost to follow-up at each step after testing. Geographic mobility is highly prevalent in SSA and represents a widespread challenge to engagement in care, but to date, has not been adequately scientifically examined to understand the magnitude of its effects on engagement in care and effectiveness of both ART as treatment and as prevention. This study will address an urgent need to understand how mobility affects HIV transmission dynamics and the care cascade, in order to optimize HIV prevention and cascade outcomes. It leverages the Sustainable East Africa Research in Community Health (SEARCH) trial (NCT# 01864603), a 6- year trial in 32 communities of 10,000 persons each to test the effectiveness of TasP for reducing community HIV incidence. This study will demonstrate novel, gender-inclusive ways to measure mobility, model the effects of mobility on HIV incidence and the care cascade, and mitigate this impact by using findings to improve HIV prevention and ART expansion for mobile populations. It will pursue three specific aims: AIM 1. Measure the mobility of individuals in eastern African communities. We will randomly select 2,400 adults from 12 SEARCH communities, stratified by intervention arm, baseline HIV status, and baseline mobility status, with n=300 per group, followed for 4 years. Every 6 months, we will collect data on mobility, including characteristics of migrants; forms (flows and types of mobility); temporicity (frequency by duration of moves); and geographic aspects (destinations, circuits, transit hubs, and their characteristics); and sexual behavior and biomarker data. With these data and trial data, we will define mobility typologies salient for prediction of a) risk behavior; b) HIV incidence; and c) HIV care cascade outcomes. AIM 2. Estimate the impact of mobility on HIV incidence. With the typologies of mobility defined above and trial outcome data, we will use to test the hypothesis that mobility attenuates the efficacy of the TasP trial to reduce 5-year HIV incidence. We will also carry out a sub-analysis with a matched cohort of 240 co-habiting couples. Annually, we will compare risk behaviors and HIV incidence in 4 mobility-defined couple types. AIM 3. Estimate the impact of mobility on the HIV care cascade. Annually, using the typologies of mobility defined above and HIV care data from trial participants, we will identify mobility typologies predictive of lapses at each step in the cascade; then estimate the contribution of mobility to lapses in care engagement. Formative translational research using participatory methods will be integrated throughout Aims 1-3, to translate findings into tangible strategies for improving HIV prevention and care among mobile populations.